Prenatal Testing For Down Syndrome Research Articles

Before you call the midwife.

The 2022 Lasker-DeBakey Clinical Medical Research Award is presented to Yuk Ming Dennis Lo of the Chinese University of Hong Kong for the discovery of fetal DNA in maternal blood, leading to development of noninvasive prenatal testing for Down syndrome.

Psychometric Assessment of the Mandarin Version of the Decisional Conflict Scale with Pregnant Women Making Prenatal Test Decisions.

PurposeWomen with high-risk pregnancies are often required to make choices about further prenatal testing for Down syndrome, but the decisional conflict they face is poorly understood. This study aimed to test the validity and reliability of the Mandarin version of the decisional conflict scale (M-DCS) in Chinese women with high-risk pregnancies making choices about further prenatal testing for Down syndrome.Patients and MethodsA methodological study was conducted to determine the psychometric properties of the M-DCS, specially, reliability and content, construct, and concurrent validity. The convenience sample comprised 240 pregnant women with high risk for Down syndrome attending the out-patient clinic of the study hospital in Guangzhou, China.ResultsThe five-factor model of M-DCS was supported by confirmatory factor analysis with a satisfactory fit to the data (RMSEA <0.08, RMR <0.05, GFI, CFI, NFI, and IFI all >0.90, except AGFI=0.88 PNFI = 0.76). The internal consistency of the M-DCS was high, with Cronbach’s α of 0.94.ConclusionThe reliability and validity (content, construct, and concurrent) of the M-DCS were all demonstrated as good. This instrument is an important tool for researchers and health-care providers working with women with high-risk pregnancies who need to make choices about further prenatal testing for Down syndrome.

What is so complicated about prenatal testing for Down syndrome? A personal view

What is so complicated about prenatal testing for Down syndrome? A personal view

Demographic Assessment of Down Syndrome: A Systematic Review.

The objective of this study is to assess the evidence about the demographic transformation of the Down Syndrome population, with a specific focus on prenatal testing, and to identify sources frequently used for demographic assessment of Down Syndrome in the world. We reviewed existing studies on demographic transformations in the population with Down Syndrome, specifically birthrate indicators, under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. The searches were made in Medline (via EBSCO Host), Academic Search Complete (via EBSCO Host), PsycINFO (via EBSCO Host), Web of Science (Core Collection), Public Health Database (via ProQuest), and The Cochrane Library. The terms were developed through Medical Subject Headings (MESH) and American Psycological Asociation Thesaurus of Psychological Index Terms (APA). Full texts were reviewed if information was given regarding location and birthrate for a range of three years or more, and if the first and last year considered was within 1960 and 2019. We found 22 references with a period of study between 1960 and 2019 following the global spread of prenatal testing for Down Syndrome. We found a consistent association between prenatal diagnosis and birthrate, enough to explain the significant fall in the prevalence of Down Syndrome, a somewhat rising incidence of Down Syndrome related to increased maternal age and extension of fertility services in healthcare systems, a generalized use of specific congenital birth defect registries as the primary source of data, and an unclear influence of socio-cultural and territorial variables. Our findings can inform research, policy, and practice to improve the reproductive health and quality of life of the population with Down Syndrome.

DEPIST 21: Information and knowledge of pregnant women about screening strategies including non-invasive prenatal testing for Down syndrome

ObjectiveTo evaluate the knowledge of pregnant women and provide information about Down syndrome (DS) screening, including non-invasive prenatal testing (NIPT). Materials and methodsA prospective unicenter study of pregnant women recruited during their first trimester foetal ultrasound was carried out. Single pregnancies from 11 to 17 + 6 weeks of amenorrhoea (SA) without a history of DS were included. “Pre” and “post” questionnaire were fulfilled before and after the consultation. Patient characteristics, prior information, information provided during the consultation, and patient satisfaction were also analysed. ResultsA total of 273 were included in the study, and 147 completed surveys (pre and post) were examined. In pre-consultation, 82 % of women know that integrated screening includes maternal serum markers and nuchal translucency (n = 103). Concerning NIPT for DS, 8% (n = 11) of women declare having been informed before the ultrasound. A minority of patients know modalities of reimbursement (n = 33, 26 %) and invasive sampling is mandatory for diagnosis when NIPT is positive (n = 37, 28 %). Significant improvement in right answers was obtained for three questions: “nuchal translucency is included in the combined screening test for DS” (p = 0,007); “blood serum markers is included in the combined screening for DS” (p = 0,009) and advanced maternal age increases risk for DS” (p = 0,004). Total score in the post questionnaire was significantly higher than the “pre” consultation questionnaire (14,7 ± 2.8 versus 14,1 ± 2.9; p = 0.01). ConclusionPatients show a high level of knowledge on screening strategies for DS in pre-consultation. They benefit from the consultation on global knowledge, NIPT, and ultrasound notions.

First-trimester screening versus non-invasive prenatal testing for Down syndrome at high-risk pregnant women in Hanoi Obstetrics and Gynecology Hospital, Vietnam: A cost-utility analysis

ABSTRACT Background: Non-invasive prenatal testing (NIPT) is a relatively new technology for diagnosis of fetal aneuploidies in the context of a developing country like Vietnam. Currently, first-trimester screening (FTS) is more conventional in Vietnam. NIPT is assumed to be more accurate than other maternal screening but is also more costly. The purpose of the study was to perform a cost-utility analysis comparing the FTS and NIPT for Down syndrome for high-risk pregnant women (over 35-year-old) in Vietnam. Methods: Decision tree model and probabilistic sensitivity analysis were used. Results: With the modelling population of 27,232 over 35 years of age pregnant women, FTS helps detect 218.5 cases of the fetus with Down syndrome compared with 247.2 cases when screening with NIPT. In addition, NIPT reduced 1384 false-positive cases compared to FTS. From a societal perspective, NIPT-dominated FTS. Compared to FTS, adopting an NIPT would cost an additional of USD 3,800 for each additional quality-adjusted life-year gained. Conclusions: NIPT is a cost-effective alternative to FTS for prenatal screening for Down syndrome with high-risk pregnant women. This is a very first attempt on cost-utility analysis of prenatal screening methods for Down syndrome in Vietnam and recommendations are made for future research to determine the most cost-effectiveness methods.

Cost-Effectiveness Analysis of Non-invasive Prenatal Testing for Down Syndrome in China.

There is little evidence in China regarding the cost-effectiveness of non-invasive prenatal testing (NIPT) for Down syndrome (DS). This study aims to evaluate the cost-effectiveness of NIPT and provide evidence to inform decision-making. To determine the cost-effectiveness of NIPT for DS, a decision-analytic model was developed using the TreeAge Pro software from a societal perspective in a simulated cohort of 10 000 pregnant women. Main indicators were based on field surveys from sampled hospitals in four locations in China and a literature review. The conventional maternal serum screening (CMSS) strategy, contingent screening strategy (NIPT delivered to high risk pregnant women after CMSS), and universal screening strategy could prevent 3.02, 7.53, and 9.97 DS births, respectively. NIPT would decrease unnecessary invasive procedures, resulting in fewer procedure-related miscarriages. The cost-effectiveness ratio of the contingent screening strategy was the lowest. When compared with the CMSS strategy, the incremental cost per DS birth averted by the contingent screening strategy and universal screening strategy were USD 20,160 and 352,388, respectively. One-way sensitivity analysis showed that, if the cost of NIPT could be decreased to USD 76.92, the cost-effectiveness ratio of the universal screening strategy would be lower than the CMSS strategy. Although NIPT has the merits of greater effectiveness and safety, CMSS is unlikely to be replaced by NIPT at this time because of NIPT's higher cost. Contingent screening may be an appropriate strategy to balance the effectiveness and cost factors of the new genetic testing technology.

Improving women\u2019s knowledge about prenatal screening in the era of non-invasive prenatal testing for Down syndrome \u2013 development and acceptability of a low literacy decision aid

BackgroundAccess to information about prenatal screening is important particularly in light of new techniques such as non-invasive prenatal testing (NIPT). This study aimed to develop and examine the acceptability of a low literacy decision aid (DA) about Down syndrome screening among pregnant women with varying education levels and GPs.MethodsWe developed a DA booklet providing information about first-trimester combined testing, maternal serum screening, and NIPT. GPs and women participated in a telephone interview to examine the acceptability of the DA and measure screening knowledge before and after reading the DA. The knowledge measure was designed to assess whether women had understood the gist of the information presented in the decision aid. It comprised conceptual questions (e.g. screening tells you the chance of having a baby with Down syndrome) and numeric questions (e.g. the accuracy of different screening tests).ResultsTwenty-nine women and 18 GPs participated. Regardless of education level, most women found the booklet ‘very’ clearly presented (n = 22, 76%), and ‘very’ informative (n = 23, 80%). Overall, women’s conceptual and numeric knowledge improved after exposure to the DA, from 4% having adequate knowledge to 69%. Women’s knowledge of NIPT also improved after receiving the decision aid, irrespective of education. Most GPs found it ‘very’ clearly presented (n = 13, 72%), and that it would ‘very much’ facilitate decision-making (n = 16, 89%).ConclusionsThe DA was found to be acceptable to women as well as GPs. A comprehensive evaluation of the efficacy of the decision aid compared to standard information is an important next step. Strategies are needed on how to implement the tool in practice.

Service provision of non-invasive prenatal testing for Down syndrome in public and private healthcare sectors: a qualitative study with obstetric providers

BackgroundCell-free fetal DNA sequencing based non-invasive prenatal testing (NIPT) for Down syndrome (DS) has become widely available. In Hong Kong, obstetric providers in the public sector refer women identified at high risk of having a child with Down syndrome to obstetric providers in the private sector for NIPT. Little is known about how the NIPT has been adopted in the public sector where DS screening is provided for free of charge. The study aimed to identify the factors influencing providers’ role enactment, such as consultation and referral, in the service provision of NIPT for DS in public and private healthcare sectors.MethodsIn-depth interviews were conducted with 20 obstetric providers offering NIPT in Hong Kong. Thematic narrative analysis was used to identify (i) the factors considered by participants when referring women for NIPT for Down syndrome in public and private healthcare sectors and (ii) their perceptions of the need to integrate NIPT into the current public antenatal service.ResultsParticipants raised concerns about the lack of transparent referral guideline between public and private sectors for NIPT. Public obstetric providers reported little obligation to provide women with much information about risks and benefits of NIPT as it was not provided by public sectors. Some private providers assumed that women referred from the public sector had already received sufficient information about NIPT. The providers were also concerned about potential application of NIPT for further detection without regulation.ConclusionsAlthough the providers had good knowledge of clinical advantages of NIPT over conventional screening, they were uncertain about how to introduce NIPT to women. Guidelines are necessary to enable better coordination of public and private sectors services to enable women to make informed choices about the uptake of NIPT.

'We would have missed out so much had we terminated': What fathers of a child with Down syndrome think about current non-invasive prenatal testing for Down syndrome.

Non-invasive prenatal testing (NIPT) allows early, accurate diagnosis of Down syndrome that has resulted in increased terminations. This qualitative study involved in-depth interviews of fathers of children with Down syndrome about their views on the availability of NIPT. Thematic network analysis revealed that although fathers appreciated an early diagnosis with NIPT, they saw the test as being a predetermined pathway to termination. Fathers felt that expectation to terminate reflects negative societal attitudes towards those with Down syndrome and disability, fearing that NIPT may become a form of eugenics. Fathers retrospectively contrasted these attitudes with the actual reality of raising their children with Down syndrome, which they described as bringing joy to their lives. Findings suggest that although fathers valued NIPT as an information-giving tool that allowed autonomous parental choices about the pregnancy, they believe that it should be accompanied by balanced information about the reality of raising a child with Down syndrome.

Talking Points: Women's Information Needs for Informed Decision-Making About Noninvasive Prenatal Testing for Down Syndrome.

Adequate knowledge is a vital component of informed decision-making; however, we do not know what information women value when making decisions about noninvasive prenatal testing (NIPT). The current study aimed to identify women's information needs for decision-making about NIPT as a first-tier, non-contingent test with out-of-pocket expense and, in turn, inform best practice by specifying the information that should be prioritized when providing pre-test counseling to women in a time-limited scenario or space-limited decision support tool. We asked women (N = 242) in Australia to indicate the importance of knowing 24 information items when making a decision about NIPT and to choose two information items they would most value. Our findings suggest that women value having complete information when making decisions about NIPT. Information about the accuracy of NIPT and the pros and cons of NIPT compared to other screening and invasive tests were perceived to be most important. The findings of this study can be used to maximize the usefulness of time-limited discussions or space-limited decision support tools, but should not be routinely relied upon as a replacement for provision of full and tailored information when feasible.

Obstetric professionals\u2019 perceptions of non-invasive prenatal testing for Down syndrome: clinical usefulness compared with existing tests and ethical implications

BackgroundWhile non-invasive prenatal testing (NIPT) for fetal aneuploidy is commercially available in many countries, little is known about how obstetric professionals in non-Western populations perceive the clinical usefulness of NIPT in comparison with existing first-trimester combined screening (FTS) for Down syndrome (DS) or invasive prenatal diagnosis (IPD), or perceptions of their ethical concerns arising from the use of NIPT.MethodsA cross-sectional survey among 327 obstetric professionals (237 midwives, 90 obstetricians) in Hong Kong.ResultsCompared to FTS, NIPT was believed to: provide more psychological benefits and enable earlier consideration of termination of pregnancy. Compared to IPD, NIPT was believed to: provide less psychological stress for high-risk women and more psychological assurance for low-risk women, and offer an advantage to detect chromosomal abnormalities earlier. Significant differences in perceived clinical usefulness were found by profession and healthcare sector: (1) obstetricians reported more certain views towards the usefulness of NIPT than midwives and (2) professionals in the public sector perceived less usefulness of NIPT than the private sector. Beliefs about earlier detection of DS using NIPT were associated with ethical concerns about increasing abortion. Participants believing that NIPT provided psychological assurance among low-risk women were less likely to be concerned about ethical issues relating to informed decision-making and pre-test consultation for NIPT.ConclusionsOur findings suggest the need for political debate initially on how to ensure pregnant women accessing public services are informed about commercially available more advanced technology, but also on the potential implementation of NIPT within public services to improve access and equity to DS screening services.

Evaluation of preferences of women and healthcare professionals in Singapore for implementation of noninvasive prenatal testing for Down syndrome.

Invasive prenatal diagnosis (IPD) has long been used to prenatally diagnose Down syndrome (DS), but it is associated with a small risk of miscarriage. Noninvasive prenatal testing (NIPT) is a highly sensitive screening test using cell-free DNA in maternal blood for detection of DS without the risk of miscarriage, but it confers a small risk of false-positive and false-negative results. The implementation of these procedures into clinical practice requires an understanding of stakeholder preferences. A total of 69 health professionals (HPs) and 301 women took part in a discrete choice experiment (DCE) in which preferences for four prenatal test attributes - accuracy, time of results, risk of miscarriage and amount of information provided - were assessed. Conditional logit regression was used to analyse the data. Data on demographics and ranked preferences for test attributes was collected, and a direct choice question regarding NIPT, IPD or neither test was posed to participants. The women showed a preference for test safety, whereas HPs prioritised test accuracy above all other attributes. When offered a direct choice of NIPT, IPD or neither test, women aged 35 years and older, those with previous miscarriage or who knew a child with DS were more likely to choose NIPT. Chinese women preferred NIPT, whereas Indian women preferred IPD. Our data highlights the need for patient-specific counselling, taking into account previous experiences and cultural factors. Since women and HPs prioritise different test attributes, it is essential that HPs recognise these differences in order to provide non-biased counselling.

Development and evaluation of training resources to prepare health professionals for counselling pregnant women about non-invasive prenatal testing for Down syndrome: a mixed methods study

BackgroundThe availability of non-invasive prenatal testing (NIPT) for aneuploidies is expanding rapidly throughout the world. Training health professionals to offer NIPT in a way that supports informed choice is essential for implementation. The aim of this study was to develop and evaluate a training package for health professionals to support the introduction of NIPT into clinical practice.MethodsTraining on NIPT was offered to health professionals, primarily midwives, involved in Down syndrome screening and testing in eight hospitals located in England and Scotland as part of a research study evaluating the implementation of NIPT in the UK National Health Service. Training was evaluated using a mixed methods approach that included quantitative questionnaires at three time points and post-training qualitative interviews. The questionnaires measured confidence, self-perceived knowledge and actual knowledge about NIPT for Down syndrome. Interviews explored opinions about the training and experiences of offering NIPT.ResultsThe training provided to the health professionals was found to positively impact on their confidence in discussing NIPT with women in their clinic, and both their perceived and actual knowledge and understanding of NIPT was improved. Knowledge remained weak in four areas; cell-free fetal DNA levels increase with gestation; turnaround time for NIPT results; cell-free fetal DNA is placental in origin; and NIPT false positive rate.ConclusionsTraining materials, including a lesson plan, PowerPoint presentation and written factsheet on NIPT, have been developed and evaluated for use in educating midwives and supporting the introduction of NIPT. Implementation of training should include a greater focus on the areas where knowledge remained low. Some groups of midwives will need additional training or support to optimise their confidence in discussing NIPT with women.

Uptake, Outcomes, and Costs of Implementing Non-invasive Prenatal Testing for Down Syndrome Into NHS Maternity Care: Prospective Cohort Study in Eight Diverse Maternity Units

(Abstracted from BMJ 2016;354:i3426) Noninvasive prenatal testing, also known as cell-free DNA (cfDNA) screening, is an efficient screening test for Down syndrome with roughly 99% sensitivity and false-positive rates of less than 0.1% in both high-risk and general populations. This study aimed to examine the potential costs and consequences of introducing cfDNA screening in the public sector Down syndrome screening pathway as an additional screening test dependent on the risk generated by current screening.

Non-invasive prenatal testing for Down syndrome in general maternity services

Since its discovery in 1997, the presence of cell-free fetal DNA in the maternal bloodstream has been put to clinical use to detect variety of fetal conditions, in the antenatal period. The use of fetal DNA can offer a highly accurate screen for the presence of Down syndrome (trisomy 21). This has numerous advantages over standard first trimester combined screening for Down syndrome; for example, a reduction in miscarriages due to its non-invasive nature. This article considers a number of issues that need to be resolved before widespread implication of this type of screening into standard NHS practice.

Decision-making for non-invasive prenatal testing for Down syndrome: Hong Kong Chinese women's preferences for individual vs relational autonomy.

Individual autonomy in antenatal screening is internationally recognized and supported. Policy and practice guidelines in various countries place emphasis on the woman's right to make her own decision and are related to concepts such as self-determination, independence, and self-sufficiency. In contrast, the dominant perspective in Chinese medical ethics suggests that the family is pivotal in making medical decisions, hence providing support for relational autonomy. This study explored Hong Kong Chinese pregnant women's preferences for individual vs relational autonomy for non-invasive prenatal testing (NIPT) for Down syndrome. A qualitative study was carried out using semi-structured interviews with 36 women who had undertaken NIPT in Hong Kong. The findings show that most Hong Kong Chinese women valued aspects of both relational and individual autonomy in decision-making for NIPT. Women expected support from doctors as experts on the topic and wanted to involve their husband in decision-making while retaining control over the outcome. Somewhat surprisingly, the findings do not provide support for the involvement of family members in decision-making for NIPT. The adequacy of current interpretations of autonomy in prenatal testing policies as an individual approach needs discussion, where policy developers need to find a balance between individual and relational approaches.

Preferences for prenatal tests for Down syndrome: an international comparison of the views of pregnant women and health professionals.

Non-invasive prenatal testing is increasingly available worldwide and stakeholder viewpoints are essential to guide implementation. Here we compare the preferences of women and health professionals from nine different countries towards attributes of non-invasive and invasive prenatal tests for Down syndrome. A discrete choice experiment was used to obtain participants' stated preference for prenatal tests that varied according to four attributes: accuracy, time of test, risk of miscarriage, and type of information. Pregnant women and health professionals were recruited from Canada, Denmark, Iceland, Israel, Italy, the Netherlands, Portugal, Singapore, and the United Kingdom. A total of 2666 women's and 1245 health professionals' questionnaires were included in the analysis. Differences in preferences were seen between women and health professionals within and between countries. Overall, women placed greater emphasis on test safety and comprehensive information than health professionals, who emphasised accuracy and early testing. Differences between women's and health professionals' preferences are marked between countries. Varied approaches to implementation and service delivery are therefore needed and individual countries should develop guidelines appropriate for their own social and screening contexts.

Decision aids that support decisions about prenatal testing for Down syndrome: an environmental scan.

BackgroundPrenatal screening tests for Down syndrome (DS) are routine in many developed countries and new tests are rapidly becoming available. Decisions about prenatal screening are increasingly complex with each successive test, and pregnant women need information about risks and benefits as well as clarity about their values. Decision aids (DAs) can help healthcare providers support women in this decision. Using an environmental scan, we aimed to identify publicly available DAs focusing on prenatal screening/diagnosis for Down syndrome that provide effective support for decision making.MethodsData sources searched were the Decision Aids Library Inventory (DALI) of the Ottawa Patient Decision Aids Research Group at the Ottawa Health Research Institute; Google searches on the internet; professional organizations, academic institutions and other experts in the field; and references in existing systematic reviews on DAs. Eligible DAs targeted pregnant women, focused on prenatal screening and/or diagnosis, applied to tests for fetal abnormalities or aneuploidies, and were in French, English, Spanish or Portuguese. Pairs of reviewers independently identified eligible DAs and extracted characteristics including the presence of practical decision support tools and features to aid comprehension. They then performed quality assessment using the 16 minimum standards established by the International Patient Decision Aids Standards (IPDASi v4.0).ResultsOf 543 potentially eligible DAs (512 in DALI, 27 from experts, and four on the internet), 23 were eligible and 20 were available for data extraction. DAs were developed from 1996 to 2013 in six countries (UK, USA, Canada, Australia, Sweden, and France). Five DAs were for prenatal screening, three for prenatal diagnosis and 12 for both). Eight contained values clarification methods (personal worksheets). The 20 DAs scored a median of 10/16 (range 6–15) on the 16 IPDAS minimum standards.DiscussionNone of the 20 included DAs met all 16 IPDAS minimum standards, and few included practical decision support tools or aids to comprehension.ConclusionsOur results indicate there is a need for DAs that effectively support decision making regarding prenatal testing for Down syndrome, especially in light of the recently available non-invasive prenatal screening tests.Electronic supplementary materialThe online version of this article (doi:10.1186/s12911-015-0199-6) contains supplementary material, which is available to authorized users.

Diagnostic tests: Non-invasive prenatal testing for Down syndrome

SUMMARY Fetal DNA can be detected in maternal plasma. This can be used to identify chromosomal and genetic abnormalities. The concentration of free fetal DNA increases with advancing gestation. Non-invasive prenatal testing should not be performed before 10 weeks. Non-invasive prenatal testing has more than 99% sensitivity and specificity for trisomy 21. It can also be used to identify trisomy 18, trisomy 13 and 45X.